Urinary Tract InfectionsPhase 3NCT03687255
Safety and Efficacy Study of Cefepime-AAI101 in the Treatment of Complicated Urinary Tract Infections
A Phase 3 study testing cefepime/AAI101 combination and Piperacillin/tazobactam in people with Urinary Tract Infections, run by Allecra at 24 sites in 19 countries.
Trial summary
Multi-center, randomized, double-blind, non-inferiority study of cefepime 2 g/AAI101 500 mg combination compared to piperacillin 4 g/tazobactam 500 mg in a population of adult patients with cUTI or AP. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Tract Infections
- What is being tested?
- cefepime/AAI101 combination and Piperacillin/tazobactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,043 participants
- Where
- 24 sitesin 19 countries
- Study dates
- 24 Sep 2018to 15 Feb 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients >18 years of age at the time of signing of informed consent;
- Expectation that the patient's cUTI or AP will require hospitalisation and initial treatment with at least 7 days of intravenous (i.v.) antibiotics;
- Female patients who are no longer of childbearing potential
- Female patients of childbearing potential must have a negative urine and/or serum pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study entry;
- Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods
- Pyuria, defined as: a. White blood cell count >10 cells/mm3 in unspun urine or ≥10 cells/high power field in spun urine sediment; or b. Urinalysis/dipstick analysis positive for leukocyte esterase;
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- Clinical signs and/or symptoms of cUTI or AP
- Have a baseline urine culture specimen obtained within 48 hours prior to randomization
- Expectation, in the judgment of the Investigator, that any implanted urinary instrumentation (e.g., nephrostomy tubes, ureteric stents, etc.) will be surgically removed or replaced before or within 24 hours after randomisation, unless removal or replacement is considered unsafe or contraindicated.
Who cannot join
- Known urine culture with Gram-positive primary pathogen at ≥105 colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional);
- History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any of the excipients used in the respective formulations, any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams), or any beta-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid);
- In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;
- Weight >180 kg;
- Concurrent infection that would interfere with evaluation of response to the study antibiotics;
- Need for or receipt of concomitant systemic antimicrobial agents after signing of informed consent, in addition to those designated in the study-treatment groups, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis;
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- Receipt of potentially effective systemic antibacterial therapy for a continuous duration of > 24 hours during the previous 72 hours before the study-qualifying baseline urine is obtained;
- Complicated urinary tract infection (UTI) known at study entry to be caused by pathogens resistant to the study antibiotics;
- Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the patient's participation in the study;
- Intractable UTI at baseline that the Investigator anticipates would require >14 days of study drug therapy;
- Complete, permanent obstruction of the urinary tract that is not anticipated to be medically or surgically relieved during i.v. study therapy and before End of Treatment (EOT);
- Gross hematuria requiring intervention other than administration of study drug or removal or exchange of a urinary catheter;
- Presence of any known or suspected disease or condition that, in the opinion of the Investigator, may confound the assessment of efficacy.
- Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic bacterial prostatitis as determined by history and/or physical examination;
- Impairment of renal function with estimated glomerular filtration rate <30 mL/min/1.73 m2 calculated by the 4-variable Modification of Diet in Renal Disease study equation,
- Urinary tract surgery within 7 days prior to randomisation or urinary tract surgery planned during the study period (except surgery required to relieve an obstruction or place a stent or nephrostomy prior to EOT);
- Any condition or circumstance that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of study data;
- Any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure and respiratory failure;
- Presence of sepsis, producing life-threatening organ dysfunction
- A QT interval corrected using Fridericia's formula >450 msec;
- Immunocompromising condition, including known history of acquired immune deficiency syndrome or known recent CD4 count <200/mm3, hematological malignancy, or bone marrow transplantation; or immunosuppressive therapy including cancer chemotherapy, medications for prevention of organ transplantation rejection, or the administration of corticosteroids ≥20 mg of prednisone or equivalent per day administered continuously for >14 days prior to randomisation;
- One or more of the following laboratory abnormalities in baseline specimens obtained at Screening: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin level >3 × upper limit of normal, or current clinically significant liver disease, including any form of known liver cirrhosis;
- One or more of the following laboratory abnormalities at Screening: platelet count <50,000/μL, absolute neutrophil count <1,000/mm3, or hemoglobin <8 g/dL;
Trial locations and contacts
24 sites in 19 countries.
24 sites in 19 countries
United States6 sites
University of New Mexico Health Sciences Center
Albuquerque, New Mexico, 87131
St. Josephs Clinical Research
Anaheim, California, 92804
Southbay Pharma Research
Buena Park, California, 90620
Mercury Street Medical
Butte, Montana, 59701
Washington University School of Medicine
St Louis, Missouri, 63110
Florida Urology Partners
Tampa, Florida, 33615
Croatia1 site
University Hospital for Infectious Diseases "Dr. Fran Mihaljevic" Department for general infectious diseases
Zagreb, 10000
Mexico1 site
Centro Especializado en Investigación Clínica S.C.
Boca del Río, CP. 94290
Poland1 site
Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych i Administracji w Warszawie, Klinika Chorob Wewnetrznych, Nefrologii i Transplantologii
Warsaw, 02-507
Slovakia1 site
Interne oddelenie, Nemocnica Malacky, Nemocnicna a.s.
Malacky, 90122
Ukraine1 site
Chernihiv City Hospital #2 of Chernihiv City Council, department of Urology
Chernihiv, 14034
About this study
Official title: A Phase 3, Randomized, Double-Blind, Study to Evaluate the Efficacy and Safety of Cefepime-AAI101 Compared to Piperacillin/Tazobactam in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis.
Multi-center, randomized, double-blind, non-inferiority study of cefepime 2 g/AAI101 500 mg combination compared to piperacillin 4 g/tazobactam 500 mg in a population of adult patients with cUTI or AP. The study will be conducted in approximately 115 sites located in the EU, the US, Central, South America and South Africa.
- Conditions
- Urinary Tract Infections
- Being tested
- cefepime/AAI101 combination, Piperacillin/tazobactam
- Medical subject headings
- Urinary Tract Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cefepime/AAI101 combinationDrug
cefepime 2 g / AAI101 500 mg
Piperacillin/tazobactamDrug
Also called PIP/TAZ
piperacillin 4 GM / tazobactam 500 MG
| Study group | Role | What they receive |
|---|---|---|
| cefepime/AAI101 combination | Experimental | Cefepime 2 g in combination with AAI101 500 mg q8h (2 hour infusion) Receives: Drug: cefepime/AAI101 combination |
| piperacillin/tazobactam | Active comparator | Piperacillin 4 g in combination with Tazobactan 500 mg q8h (2 hour infusion) Receives: Drug: Piperacillin/tazobactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients in the Microbiological Modified Intent to Treat (m-MITT) Population who achieve overall treatment success at Test Of Cure (TOC)
Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (<103 CFU/mL in urine culture).
Measured: 7 days after EOT [±2 days] for patients receiving 7 days of treatment and 19 days after randomization [±2 days] for patients receiving more than 7 days of treatment.
Secondary outcomes (1)
Proportion of patients in the m-MITT Population with overall treatment success at End of Treatment (EOT)
Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (<103 CFU/mL in urine culture).
Measured: 7 days for patients with cUTI only and up to 14 days for patients cUTI and blood stream infections
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2018
- Study start24 Sep 2018
- Primary completion30 Jan 2020
- Study completion15 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Urinary Tract InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,043 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allecra
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03687255
- Sponsor's protocol ID
- AT-301
- Status last verified
- Mar 2020
- First submitted
- 26 Sep 2018
- Last updated
- 10 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chandra P. Cefepime-enmetazobactam for complicated urinary tract infections: Redefining ESBL therapy. Indian J Med Res. 2026 Feb;163(2):183-193. doi: 10.25259/IJMR_2073_2025.
PubMed 41949135Kaye KS, Belley A, Barth P, Lahlou O, Knechtle P, Motta P, Velicitat P. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022 Oct 4;328(13):1304-1314. doi: 10.1001/jama.2022.17034.
PubMed 36194218
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Study to Evaluate the Efficacy and Safety of Cefepime-AAI101 Compared to Piperacillin/Tazobactam in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis.
- ClinicalTrials.gov ID
- NCT03687255
- Acronym / sponsor ID
- AT-301
- Conditions
- Urinary Tract Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,043 participants (actual)
- Lead sponsor
- AllecraIndustry (pharma, biotech, devices)
- Collaborators
- Medpace, Inc.
- Study start
- 24 Sep 2018 (actual)
- Primary completion
- 30 Jan 2020 (actual)
- Study completion
- 15 Feb 2020 (actual)
- First posted
- 27 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multi-center, randomized, double-blind, non-inferiority study of cefepime 2 g/AAI101 500 mg combination compared to piperacillin 4 g/tazobactam 500 mg in a population of adult patients with cUTI or AP. The study will be conducted in approximately 115 sites located in the EU, the US, Central, South America and South Africa.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cefepime/AAI101 combination | Experimental | Drug: cefepime/AAI101 combinationCefepime 2 g in combination with AAI101 500 mg q8h (2 hour infusion) |
| piperacillin/tazobactam | Active comparator | Drug: Piperacillin/tazobactamPiperacillin 4 g in combination with Tazobactan 500 mg q8h (2 hour infusion) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female patients >18 years of age at the time of signing of informed consent;
- Expectation that the patient's cUTI or AP will require hospitalisation and initial treatment with at least 7 days of intravenous (i.v.) antibiotics;
- Female patients who are no longer of childbearing potential
- Female patients of childbearing potential must have a negative urine and/or serum pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study entry;
- Male patients, female patients receiving hormone replacement therapy (HRT), and female patients of childbearing potential must agree to use highly effective contraception methods
Key exclusion criteria (23 listed)
- Known urine culture with Gram-positive primary pathogen at ≥105 colony-forming units (CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note: Gram staining is optional);
- History of significant hypersensitivity or allergic reaction to cefepime, piperacillin/tazobactam, any of the excipients used in the respective formulations, any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams), or any beta-lactamase inhibitors (e.g., tazobactam, sulbactam, or clavulanic acid);
- In the opinion of the Investigator, the patient is considered unlikely to survive the approximately 6-week study period;
- Weight >180 kg;
- Concurrent infection that would interfere with evaluation of response to the study antibiotics;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cefepime/AAI101 combinationcefepime 2 g / AAI101 500 mg | Drug | cefepime/AAI101 combination |
| Piperacillin/tazobactamAlso: PIP/TAZpiperacillin 4 GM / tazobactam 500 MG | Drug | piperacillin/tazobactam |
Primary outcome
Proportion of patients in the Microbiological Modified Intent to Treat (m-MITT) Population who achieve overall treatment success at Test Of Cure (TOC)
Time frame: 7 days after EOT [±2 days] for patients receiving 7 days of treatment and 19 days after randomization [±2 days] for patients receiving more than 7 days of treatment.
Treatment success is defined as the composite of clinical outcome of Cure and the microbiological outcome of Eradication (<103 CFU/mL in urine culture).
1 secondary outcome
Proportion of patients in the m-MITT Population with overall treatment success at End of Treatment (EOT)
Time frame: 7 days for patients with cUTI only and up to 14 days for patients cUTI and blood stream infections
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- Derived from this study: PubMed 41949135Chandra P. Cefepime-enmetazobactam for complicated urinary tract infections: Redefining ESBL therapy. Indian J Med Res. 2026 Feb;163(2):183-193. doi: 10.25259/IJMR_2073_2025.
- Derived from this study: PubMed 36194218Kaye KS, Belley A, Barth P, Lahlou O, Knechtle P, Motta P, Velicitat P. Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial. JAMA. 2022 Oct 4;328(13):1304-1314. doi: 10.1001/jama.2022.17034.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
24 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cefepime/AAI101 combination and Piperacillin/tazobactam in people with Urinary Tract Infections, run by Allecra at 24 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States, Argentina, Belarus, Bulgaria, Croatia and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients in the Microbiological Modified Intent to Treat (m-MITT) Population who achieve overall treatment success at Test Of Cure (TOC) (time frame: 7 days after EOT [±2 days] for patients receiving 7 days of treatment and 19 days after randomization [±2 days] for patients receiving more than 7 days of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03687255, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2020.